A fully functional, productive infectious disease aerobiology core is a critical lynchpin in any biodefensefocused research laboratory. Aerosol exposure is the most probable route of infection in a biological warfare or terrorist attack. The design of the NEIDL incorporates both BSL-3 and BSL-4 Aerobiology Core laboratories. We believe that this design maximizes the efficiency of research that will be performed under high containment in the Institute by minimizing the extensive downtime that would be required for conversion of a single flexible laboratory module. Moreover, this design allows for concomitant use of both high containment laboratories, thereby increasing by more than 2-fold the total work flow in this Core. For example, an aerosol challenge study to test the efficacy of a capsule-conjugate vaccine for Francisella tularensis could be conducted in the BSL-3 Aerobiology Core laboratory at the same time a Kyasanur forest disease challenge study (as is proposed in the Collaborative Research Group Core #1) is conducted in the BSL-4 Aerobiology Core. With a single flexible laboratory housing the Core, these experiments would, by design, have to be conducted sequentially. This would result in considerable down time for decontamination, and re-certification following conversion from BSL-3 to BSL-4, or visa versa, to meet standards. From an operational perspective, not all personnel trained for work in the BSL-3 Aerobiology Core will necessarily have to be certified to work under BSL-4 containment. While some personnel will have clearance to work in either laboratory, it is clear that the Standard Operating Procedures (SOPs), types of organisms (BSL-3, the bacterial pathogens Francisella tularensis, Yersinia pestis, multi-resistant Mycobacterium tuberculosis', versus BSL-4, viral pathogens Ebola, Marburg, KFD, Lassa), decontamination procedures, and operational plans will be appropriate for each level of containment. Research and development of medical products against biological threat agents, pathogenesis studies, and diagnostics studies all begin with well-characterized exposure modalities relevant to the expected route of exposure in the human condition. Controlled experimental infection allows the researcher to exert control over a wide range of experimental parameters in order to generate a biological response in a group of animals exposed to a similar dose. Design and operation of the laboratory core to support this type of experimentation is technically and logistically demanding;coordination between the biological and engineering sciences is critical to successful aerobiology research. A BSL-3 aerobiology core program as a component of the NEIDL is therefore a critical necessity to support the NIAID biodefense research agenda.